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Performance of a ⁶²Zn/⁶²Cu Generator in Clinical Trials of PET Perfusion Agent ⁶²Cu-PTSM

Proportional Technologies, Inc., Houston, Texas
Purdue University, West Lafayette, Indiana

Correspondence: For correspondence or reprints contact: Jeffrey L. Lacy, PhD, Proportional Technologies, Inc., 8010 El Rio, Houston, TX 77054.

ABSTRACT

The ⁶²Zn/⁶²Cu PET generator can be inexpensively produced and distributed from a single production site operating under typical good manufacturing practice guidelines. It therefore has the potential to greatly facilitate development of clinically practical PET. We report generator performance in a study in which ⁶²Cu-pyruvaldehyde-bis(n4-methylthiosemicarbazone (PTSM) myocardial perfusion imaging is compared with ^99mTc-sestamibi in the diagnosis of coronary artery disease. The ⁶²Zn/⁶²Cu generator is an improved version of a previously reported system that employs automated synthesis of ⁶²Cu-PTSM. With this approach, the cumbersome step of ¹⁸C purification has been eliminated. Methods: The ⁶²Zn (9.3 h half-life) parent isotope is prepared by proton bombardment of natural copper at 33 MeV. A typical target irradiated with 37.5 µA/h is delivered by 12:00 PM on the day it is to be processed. Purified ⁶²Zn obtained from the target is loaded onto the generator column in 2 mol/L HCI. The generator is eluted using an internal three-channel peristaltic pump, which delivers 2.25 mL eluant (1.8 mol/L NaCl, 0.2 mol/L HCl) through the generator column to elute the ⁶²Cu in 40 s. The same pump simultaneously pumps an equal volume of buffer (0.4 mol/L NaOAc) and 1 mL ligand solution (2 ppm PTSM, 2% EtOH) passing it through a septum into a 35-cc syringe preloaded with 28 mL sterile water. This solution is thoroughly mixed by agitation of the syringe and injected as a bolus through a 0.2 µm filter. The generator is eluted twice before shipping, providing quality assurance samples, and shipped to the clinical site by overnight delivery. Complete quality assurance testing is performed the evening before the generator reaches the clinical site. Results: A total of 34 generators have been produced and shipped to 2 clinical sites for a phase III Food and Drug Administration study. The load activity on the generators at 8:00 AM the day of clinical use was 1.7 ± 0.2 GBq (46.7 ± 5.6 mCi), and yield was 72% ± 16%. Breakthrough of ⁶²Zn was undetectable by high-purity germanium spectroscopy for all units. Radiochemical purity was 95.4% ± 2.4%. Volume delivered, pH, sterility, and bacterial endotoxin tests yielded passing results on all generators. The entire process of generator production, from target receipt to generator shipment, took less than 6 h and cost approximately $1000, including shipping charges and cyclotron cost. A total of 68 patients were injected with 2 ⁶²Cu-PTSM doses, with a mean injected activity of 0.8 ± 0.2 GBq (20.5 ± 5.3 mCi) with no adverse side effects. Conclusion: Results of this work confirm that the ⁶²Zn/⁶²Cu generator is an easily produced, transportable, and inexpensive source of PET radiopharmaceuticals, which can expand the field of clinical PET imaging by providing radiopharmaceuticals to sites not associated with cyclotrons.

Key Words: PET radiopharmaceuticals • ⁶²Zn/⁶²Cu generator • pyruvaldehyde-bis(n4-methylthiosemicarbazone) • myocardial perfusion

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